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. 2022 Sep 1;14(17):4286.
doi: 10.3390/cancers14174286.

Prognostic Capability of TNBC 3-Gene Score among Triple-Negative Breast Cancer Subtypes

Jhajaira M Araujo  1   2 , Gabriel De la Cruz-Ku  3   4 , Melanie Cornejo  1 , Franco Doimi  5 , Richard Dyer  5 , Henry L Gomez  6 , Joseph A Pinto  1
Affiliations

Prognostic Capability of TNBC 3-Gene Score among Triple-Negative Breast Cancer Subtypes

Jhajaira M Araujo et al. Cancers (Basel). .

Abstract

Background: Triple-negative breast cancer (TNBC) is a complex and molecularly heterogeneous entity, with the poorest outcome compared with other breast cancer subtypes. Previously, we developed a TNBC 3-gene score with a significant prognostic capability. This study aims to test the 3-gene score in the different TNBC subtypes. Methods: Data from 204 TNBC patients treated with neoadjuvant chemotherapy were retrieved from public datasets and pooled (GSE25066, GSE58812, and GSE16446). After removing batch effects, cases were classified into Lehman’s TNBC subtypes and then the TNBC 3-gene score was used to evaluate the risk of distant recurrence in each subgroup. In addition, the association with tumor-infiltrating lymphocyte (TILs) levels was evaluated in a retrospective group of 72 TNBC cases. Results: The TNBC 3-gene score was able to discriminate patients with different risks within the pooled cohort (HR = 2.41 for high vs. low risk; 95%CI: 1.50−3.86). The score showed predictive capability in the immunomodulatory subtype (HR = 4.16; 95%CI: 1.63−10.60) and in the mesenchymal stem-like subtype (HR = 18.76; 95%CI: 1.68−208.97). In the basal-like 1, basal-like-2, and mesenchymal subtypes, the observed differential risk patterns showed no statistical significance. The score had poor predictive capability in the luminal androgen receptor subtype (p = 0.765). In addition, a low TNBC 3-gene score was related to a high level of TIL infiltration (p < 0.001). Conclusions: The TNBC 3-gene score is able to predict the risk of distant recurrence in TNBC patients, specifically in the immunomodulatory and mesenchymal stem-like subtype. Despite a small sample size in each subgroup, an improved prognostic capability was seen in TNBC subtypes with tumor-infiltrating components.

Keywords: DRFS; TNBC; prognostic biomarkers; survival.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Distribution of Triple Negative Breast Cancer subtypes in each dataset, GSE25066 (n = 80), GSE58812 (n = 83) and GSE16446 (n = 41). Abbreviations: basal-like 1 (BL1), basal-like 2 (BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal stem-like (MSL), and luminal androgen receptor (LAR).
Figure 2
Figure 2
Survival curves of 204 Triple negative breast cancer (TNBC) patients. (A) Distant recurrence free survival (DRFS) of TNBC patients stratified by the 3-genes score using the median as cutoff. (B) DRFS for patients stratified by molecular TNBC subtype. Abbreviations: basal-like 1 (BL1), basal-like 2 (BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal stem-like (MSL), and luminal androgen receptor (LAR).
Figure 3
Figure 3
Distribution of the 3-genes score in each TNBC subtype. Lower values were observed in the IM and MSL subtype. Asterisks represent statistical significance (* p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001).
Figure 4
Figure 4
Three genes signature as prognostic factor of DRFS in TNBC subtypes. The 3 genes-score was statistically significant in the immunomodulatory and mesenchymal stem-like subtypes.
Figure 5
Figure 5
Comparison of the Three genes risk score according to TILs group. Patients with low TILs had a higher score. Asterisks represent statistical significance level (*** p < 0.001).
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